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Related Concept Videos

Non-LTR Retrotransposons03:18

Non-LTR Retrotransposons

As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
LTR Retrotransposons03:08

LTR Retrotransposons

LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
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Retrovirus Life Cycles

Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the retrovirus to...
Viral Mutations00:36

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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material for adaptive...
Size and Structure of Viral Genomes01:26

Size and Structure of Viral Genomes

Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...

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Drastic decrease of transcription activity due to hypermutated long terminal repeat (LTR) region in different HIV-1

Eva Ramírez de Arellano1, José Alcamí, Marisa López

  • 1Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain; National Center for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.

Antiviral Research
|August 18, 2010
PubMed
Summary

HIV-1 gene expression relies on long terminal repeat (LTR) interactions. G to A hypermutation in LTR sequences significantly impairs viral promoter activity, reducing gene transcription.

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Area of Science:

  • Virology
  • Molecular Biology
  • Genetics

Background:

  • HIV-1 gene expression is regulated by interactions between viral and cellular transcription factors at the long terminal repeat (LTR) sequences.
  • Understanding HIV-1 LTR variability is crucial for comprehending viral gene expression and potential therapeutic targets.

Purpose of the Study:

  • To investigate HIV-1 subtyping and nucleotide variability within the LTR region.
  • To determine the impact of LTR variability and specific mutations on HIV-1 transcriptional activity.

Main Methods:

  • HIV-1 subtyping and nucleotide sequencing of LTR and protease (PR) genes from clinical samples.
  • Cloning of LTR sequences into luciferase-expression vectors.
  • Assessing basal and Tat- and PMA-induced transcriptional activities in vitro.

Main Results:

  • A high frequency (37.8%) of recombinant HIV-1 sequences at LTR/PR regions were identified.
  • All HIV-1 LTRs showed low basal activity, inducible by Tat and PMA, with variations observed across subtypes.
  • Subtypes C and CRF01_AE LTRs exhibited higher transcriptional activity compared to the HXB2 clade B promoter.
  • G to A hypermutation within LTR significantly compromised promoter activity and luciferase gene transcription.

Conclusions:

  • HIV-1 LTR sequences exhibit significant variability and recombination, influencing viral gene expression.
  • Specific mutations, particularly G to A hypermutation, can severely impair HIV-1 LTR promoter function.
  • LTR variability and mutational patterns are critical factors in HIV-1 pathogenesis and require further investigation.